Malignant brain tumors remain incurable and improving outcomes will require personalized treatment strategies. In personalized medicine, therapeutics are tailored to each tumor. To apply personalized medicine to brain tumors, a more thorough understanding of therapeutically actionable tumor features in individuals and patient cohorts is needed. Actionable tumor features include genetic mutations, aberrantly expressed proteins, and tumorigenic microenvironment elements. In brain tumors, applying personalized treatment strategies is complicated by multi-layered heterogeneity, biological complexity, and difficult drug delivery. In this dissertation I investigated factors that currently hinder the use of personalized medicine for malignant brain tumors.